Journal
NATURE PROTOCOLS
Volume 14, Issue 6, Pages 1884-1925Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41596-019-0168-0
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Funding
- MRC-Sackler Doctoral Training Partnership
- Addenbrooke's Charitable Trust Grant
- Academy of Medical Sciences Clinical Lecturer Starter Grant [SGL019/1071]
- NIHR
- EPSRC [EP/R511675/1, EP/N509620/1]
- Isaac Newton Trust
- EASL PhD Juan Rodes Studentship
- ERC Proof of Concept grant Relieve-Chol
- Cambridge University Hospitals National Institute for Health Research Biomedical Research Centre
- ERC advanced grant New-Chol
- Wellcome Trust
- Medical Research Council of the Wellcome-Medical Research Council Cambridge Stem Cell Institute
- Rosetrees Trust [REAG/240, NMZG/233]
- Norwegian PSC Research Center
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Pediatric liver transplantation is often required as a consequence of biliary disorders because of the lack of alternative treatments for repairing or replacing damaged bile ducts. To address the lack of availability of pediatric livers suitable for transplantation, we developed a protocol for generating bioengineered biliary tissue suitable for biliary reconstruction. Our platform allows the derivation of cholangiocyte organoids (COs) expressing key biliary markers and retaining functions of primary extra- or intrahepatic duct cholangiocytes within 2 weeks of isolation. COs are subsequently seeded on polyglycolic acid (PGA) scaffolds or densified collagen constructs for 4 weeks to generate bioengineered tissue retaining biliary characteristics. Expertise in organoid culture and tissue engineering is desirable for optimal results. COs correspond to mature functional cholangiocytes, differentiating our method from alternative organoid systems currently available that propagate adult stem cells. Consequently, COs provide a unique platform for studies in biliary physiology and pathophysiology, and the resulting bioengineered tissue has broad applications for regenerative medicine and cholangiopathies.
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